In our current investigations, we demonstrated that patients with idiopathic Raynaud's disease have increased alpha-adrenergic receptor sensitivity and/or density compared to age and sex-matched controls. Much recent animal research shows that local cooling potentiates alpha2 receptor mediated vasoconstriction in cutaneous blood vessels. We now propose to determine if this potentiation occurs to a greater extent in idiopathic Raynaud's patients than in normal persons. Although a genetic etiology has been suggested for Raynaud's disease, it has never been systematically investigated. We propose to examine the familial occurrence of Raynaud's in a controlled study. Using selective digital nerve blocks and intra-arterial infusions of propranolol, we found that vasodilation during temperature feedback is mediated-through a beta-adrenergic mechanism and not through efferent digital nerves. The role of circulating catecholamines in feedback-induced vasodilation has never been examined, but could provide a plausible physiological basis for this mechanism. We propose to measure circulating catecholamines in controlled studies of Raynaud's disease patients and normal persons. In the course of our work on adrenoceptors in Raynaud's disease, we discovered that the sensitivity and/or density of peripheral vascular alpha and beta-adrenergic receptors is significantly lower in normal women than in normal men. In light of sex differences in the incidence of many vascular diseases, it is important to determine the physiological significance of these findings and the mechanisms which underlie them. We propose to examine the role of the sympathetic nervous system and the menstrual cycle in modulating vascular adrenergic receptors in women. Since we have only studied sex differences in adrenoceptors in a cutaneous vascular bed, we propose to determine if our findings extend to the muscle circulation as well.